Introduction

• The course is focused on modeling of biological processes at

cell and molecular levels.

• Good in math is not necessarily good in modeling.

- Solving equations vs setting up equations

• What is mathematical modeling?

Various Definitions in the literature

• The basic idea of mathematical modeling is to find a mathematical

relationship that behaves in the same ways as the objects or
processes under investigation.

• It is to approximate a real world system, (e.g., cell), using

mathematical equations, that the prediction can be tested against
observable properties of the system. Therefore, the sophistication
of the model depends on techniques that are available for making
observations of the system.

• A useful mathematical model may give insight about how

something really works, and predict new things that cannot be
predicted through intuition. (e.g., blackbox => greybox)

• It can provide a powerful means of integrating several pieces of

knowledge at a given level to describe responses at a higher
organizational level. (e.g., molecule => cell => tissue => whole body)

Examples of biological processes

• Signal transduction in cells

• Receptor-mediated endocytosis of proteins
• Glucose uptake by cells
• Na/K pump
• Regulation of enzymatic reactions
• Regulation of gene expression
• Equilibrium DNA binding
• Hemoglobin/oxygen binding
• etc.

1
 How to model biological systems

Modeling

Nature’s laws Experimental data Hypotheses

- 1st law - Determine model - e.g., rate of

constants change in this
course
- 2nd law - Verify model predictions

- Establish empirical
(In general, it
- Mass cannot be
relationships in the
conservation model covered in this
course since it
is an art.)

How to model biological systems (Cont.)

Analytical solution or numerical
simulation
Model
- Validate the model by comparing model
predictions with experimental data

• Math model for a given biological process is not unique but they all have to
‐ satisfy Nature’s laws
‐ be consistent with certain if not all expt data
‐ be self‐consistent

e.g. Model 2
Model 1
(assuming B >> C)
B
A B A
C
dA dA
 BC B
dt dt

Biological Systems at Multiple Scales

Body level
(L = 1 m)

Organ level
(L = 10-3 – 10-1 m)

Tissue and
Cell levels
(L = 10-5 – 10-4 m)

Molecular level
(L = 10-9 – 10-7 m)

2
 
Multi-Scale Modeling 
F  F   
   (D  F )       ( F  v )r sin( )dV
t K  exp( F  r )

Advantage:
- Providing detailed analysis
of a system.
Body - Revealing mechanisms

Challenges:
- Knowing detailed information
Tissue of the system.
Multi-scales - Dealing with complex system
and nonlinear interactions
Cell Feasibility:
- 5-6 orders of magnitude
changes in spatial and
Molecule temporal scales for simple
systems.
- 2-3 orders of magnitude
changes for complex
systems.

Thermodynamic Modeling

1st and 2nd laws

Input Output 1st and 2nd laws
(Mass) = 0 Input (Mass) = 0 Output

Input
1st and 2nd laws Output
(Mass) = 0

Input 1st and 2nd laws Output

(Mass) = 0
1st and 2nd laws
Input (Mass) = 0 Output

Images are from http://en.wikipedia.org/

Thermodynamic Modeling (Cont.)

Advantage:

- A general approach to modeling of different systems (e.g., 2nd law is

the most general idea in science and engineering).

- Providing average properties of the systems (e.g., H, U, S, G).

Disadvanges:

- Phenomenological and cannot provide structural mechanisms

- Cannot provide detailed information on the system.

- The concepts are abstract.

If multiscale modeling is not feasible, thermodynamic

modeling is an alternative approach.

Or, thermodynamic modeling can be a starting point in modeling,

and some molecular mechanisms can be added to the model.

3
 Example of Advanced Modeling

Molecular collision in
an isolated system

Multiscale modeling Thermodynamic modeling

- based on Newton’s - based on 1st and 2nd laws
laws of motion - U = 0 and G < 0
- the analysis is done
for each molecules

Abstract versus Simple concepts

1. At macroscopic level

Simple, specific concepts: age, name, height, color, cloth, species, …..
Abstract, general concepts: animals, S, G, U, H

2. At microscopic level

Simple, specific concepts: cytoskeleton, membrane, red blood cell, etc, …..
Abstract, general concepts: cell or molecular systems, S, G, U, H

"The trouble with simple things is that one must understand them very well.“

- Anonymous